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INHIBITION OF NAD(P)H OXIDASE REDUCES FIBRONECTIN EXPRESSION IN STROKE‐PRONE RENOVASCULAR HYPERTENSIVE RAT BRAIN
Author(s) -
Cui Chunmei,
Chen Alex F,
Jiang Zongpei,
Wu Qingqing,
Lin Jianwen,
Wen Hongmei,
Zeng Jinsheng
Publication year - 2007
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04554.x
Subject(s) - renovascular hypertension , stroke (engine) , fibronectin , nad(p)h oxidase , nad+ kinase , medicine , chemistry , cardiology , oxidase test , endocrinology , blood pressure , biochemistry , enzyme , extracellular matrix , mechanical engineering , engineering
SUMMARY1 The aim of the present study was to test the hypothesis that in vivo chronic inhibition of NAD(P)H oxidase reduces cerebrovascular fibronectin expression in stroke‐prone renovascular hypertensive rats (RHRSP). 2 The RHRSP model was induced by two clips and NAD(P)H oxidase was inhibited with apocynin. The mRNA and protein expression of NAD(P)H oxidase subunit p22 phox in brains of RHRSP and Sprague‐Dawley (control) rats was determined using real‐time reverse transcription–polymerase chain reaction, western blot and immunohistochemistry. The expression of fibronectin protein was localized immunohistochemically in cerebral vessels and then quantified by western blot. 3 Cerebrovascular fibronectin levels in RHRSP ( n = 6) were significantly higher than control ( n = 5) levels 8 weeks after operation (1.29 ± 0.04 vs 1.15 ± 0.02, respectively; P = 0.007). The p22 phox immunopositive reactivity was localized in the cerebral vasculature of control rats and RHRSP. Furthermore, chronic treatment of RHRSP with apocynin, a selective NAD(P)H oxidase inhibitor, in the drinking water for 4 weeks (1.5 mmol/L, 5 weeks after operation) resulted in a significant decrease in the expression of p22 phox protein (0.85 ± 0.01 vs 0.93 ± 0.01 in non‐treated RHRSP; n = 5; P = 0.002), with a concomitant reduction of fibronectin levels in the cerebral vasculature (1.31 ± 0.03 vs 1.56 ± 0.05 in non‐treated RHRSP; n = 5; P = 0.002). No significant differences were detected in the expression of p22 phox mRNA and protein between RHRSP (4 and 8 weeks after renal artery constriction) and the control group. 4 These findings suggest that the chronic inhibition of NAD(P)H oxidase in vivo by apocynin reduces cerebrovascular fibronectin levels, which may lessen hypertensive cerebrovascular fibrosis.